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Schizophrenia Research Forum

Subtle yet widespread disruptions in gene expression mark the brain in schizophrenia, according to a study of over 500 brain samples published in Nature Neuroscience on September 26. From the CommonMind Consortium, the study sequenced RNA messages to provide the most comprehensive picture yet of gene expression in the brain in schizophrenia.

Schizophrenia cost the US an extra $155.7 billion in 2013, according to a study published in the Journal of Clinical Psychiatry. This economic burden far exceeds a 2002 estimate, with the bulk due to indirect costs, including loss of productivity due to unemployment or caregiving. This finding signals a need for therapies that ameliorate cognition or otherwise help functioning in people with schizophrenia.

Transcripts in the brain have identified likely risk genes for schizophrenia along chromosome 10, according to a paper published May 9 in Nature Medicine. Led by Daniel Weinberger of the Lieber Institute for Brain Development in Baltimore, Maryland, in collaboration with pharmaceutical company AstraZeneca, the researchers sequenced RNA messages in brain to find associations between transcripts and risk alleles identified by previous genetic studies. This turned up a link to a gene called BORCS7 and a novel, human-specific form of the AS3MT gene.

The study illustrates the information bonanza within transcript data, which measures gene expression levels and splice variants. This approach can pick up where genetic studies have left off: for example, genomewide association studies (GWAS) that survey common genetic variants, called single nucleotide polymorphisms (SNPs), have cast suspicion upon the 10q24.32 region that is chock-a-block with genes, but stopped short of deciphering the true culprits.

Two studies of DNA methylation offer more evidence that the way genes are turned on and off could be a source of risk for schizophrenia. Methyl groups placed on genes suppress their action, and people vary somewhat in the particular genes manufactured into proteins. Though both studies indicate a role for methylation in schizophrenia, the specifics remain unclear.